Thrombosis in Extracorporeal Membrane Oxygenation (ECMO) Circuits

Abstract

Thrombosis in extracorporeal membrane oxygenation (ECMO) circuits remains a frequent complication. We characterize the location, extent, structure, and clinical implications of thrombi in 53 ECMO circuits from 46 pediatric patients. The tubing, pump, and oxygenator were examined for visible thrombi. Representative samples of thrombi were collected for histologic, immunofluorescence, and immunohistochemical analysis. Thrombi were found in 81% of ECMO circuits. The most clinically significant were inflow oxygenator membrane surface thrombi (11% of circuits), arterial tubing thrombi (30%), and venous tubing (26%) or connector thrombi (26%). Oxygenator membrane surface thrombi resulted in rapidly increasing delta pressure across the oxygenator over 1-2 days, oxygenator failure, and circuit replacement. Oxygenator membrane surface thrombi were associated with intravascular venous thrombosis and bacterial infection before starting ECMO. Arterial cannula/tubing thrombi led in one case to aortic and mesenteric artery thrombosis followed by bowel infarction. In 11% of cases, venous tubing thrombi grew large enough to break off and embolize to the pump, resulting in increased hemolysis. Antifibrinolytic therapy during ECMO was associated with an increased risk of pump thromboembolism. Other less clinically significant thrombi included pump axle thrombi with thrombus fragments trapped in the oxygenator (45%), and deep oxygenator membrane thrombi (15%). Examination of ECMO circuits after removal is a useful quality improvement tool that can elucidate the cause of circuit problems, indicate patients at increased risk of thrombosis, and suggest areas for possible improvements.

Thrombus formation during ECMO: Insights from a detailed histological analysis of thrombus composition

“…Our histological data, however, indicates that both the individual thrombus components (RBCs, fibrin, platelets, and VWF content) and the unbiased thrombus cluster-types are not associated with the respective location in the device. Similar as to our quantitative findings, a recent descriptive report, investigating 53 pediatric ECMO circuits, has shown that thrombi originating from different device locations consist of a mixture of fibrin, platelets, red blood cells, VWF, and leukocytes 19. In contrast, two descriptive reports by Hastings et al have shown that oxygenator and tubing thrombi mainly consist of RBCs and fibrin,…”

“…The exact mechanisms of in‐device ECMO thrombosis remain poorly understood. Yet, only few studies investigated the composition of ECMO thrombi 14,15,19 . These reports mainly focused on the descriptive analysis of ECMO thrombi in a pediatric population, in particular RBC, fibrin, platelets, and VWF content, and will be compared with our findings throughout the discussion 14,15,19 .…”

“…Yet, only few studies investigated the composition of ECMO thrombi. 14,15,19 These reports mainly focused on the descriptive analysis of ECMO thrombi in a pediatric population, in particular RBC, fibrin, platelets, and VWF content, and will be compared with our findings throughout the discussion. 14,15,19 Various elements are thought to contribute to ECMO thrombus formation, and good understanding of this multifactorial thrombogenicity can help design better therapeutic prevention strategies and circuit technologies.…”

The microfluidic artificial lung: Mimicking nature's blood path design to solve the biocompatibility paradox

“…11,12 In addition, thrombosis of the oxygenator membrane can lead to failure of the ECMO circuit, the need for frequent circuit changes, and the use of high doses of anticoagulation medications, further endangering the patient and adding a significant economic burden to the hospital/ healthcare system. 13,14 The contact of blood with extracorporeal surfaces can also lead to a robust inflammatory reaction characterized by high levels of pro-inflammatory cytokines, initiation of the complement system, stimulation of neutrophils and platelets, injury to endothelial cells and capillaries, and ultimately, worsening lung and extrapulmonary organ damage. 12,[15][16][17][18][19] This pro-inflammatory response is closely linked to an activation of the intrinsic and extrinsic coagulation pathways, creating a "thromboinflammatory" state, an effect that has been particularly prevalent in patients infected with COVID-19.…”

“…Exposure of blood to the extracorporeal circulation/surfaces leads to activation of the coagulation cascade, platelet dysfunction, and hemolysis, resulting in both clotting and bleeding complications for the patient 11,12 . In addition, thrombosis of the oxygenator membrane can lead to failure of the ECMO circuit, the need for frequent circuit changes, and the use of high doses of anticoagulation medications, further endangering the patient and adding a significant economic burden to the hospital/healthcare system 13,14 …”